Comparison of Sevikar® and the Combination of Perindopril/Amlodipine on Central Blood Pressure

Hypertension Clinical Trial

Official title:

Efficacy of Sevikar® Compared to the Combination of Perindopril/ Amlodipine on Central Arterial Blood Pressure in Patients With Moderate to Severe Hypertension-

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01101009
• Other study ID #: DSE- SEV-02-09
• Secondary ID: 2009-012966-30
• Status: Completed
• Phase: Phase 4
• Start date: April 2010
• Est. completion date: December 2012

Study information

• Verified date: January 2013
• Source: Daiichi Sankyo, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Comparison of the combination of amlodipine with an angiotensin receptor blocker or an angiotensin converting inhibitor, on central arterial blood pressure in patients with hypertension and additional risk factors. This is a randomised, double-blind, double-dummy, multicenter study. The duration of active treatment 24 weeks.

Description:

The study, multi-center balanced, parallel group (two treatment arms), randomized, double-blind (double-dummy), non-inferiority study is designed to show non-inferiority of Sevikar® (olmesartan(OM)/amlodipine (AM)) 40/10 mg compared to the combination of Perindopril (PER) 8 mg plus Amlodipine 10 mg with regard to central systolic blood pressure lowering effect, using the change from baseline (Week 0) to final examination (Week 24).

Male and female Caucasians aged ≥ 40 years and <80 years with moderate to severe hypertension, defined by a systolic blood pressure (SBP) ≥ 160 and ≤ 200 or diastolic blood pressure (DBP) ≥ 100 and ≤ 115 mmHg for untreated patients, SBP ≥ 140 or DBP ≥ 90 mmHg for insufficiently pre-treated patients and SBP ≥ 130 mmHg or DBP ≥ 80 mmHg for insufficiently pretreated diabetics chronic kidney disease will be eligible for participation. In addition,three additional risk factors should be present.

During the course of the study three central blood pressure measurements (at randomization, at week 12 and at termination) will be performed with SphygmoCor ultrasound method. The conventional measurements with calibrated tensiometers (Omron) will be performed at each visit. Ambulatory blood pressure monitoring will be performed at randomisation.

The study starts with a 2-4 week run in phase. AM will be given as open-labelled 5 mg or 10 mg tablets, administered once daily. After randomization during the double-blind phase, study medication will comprise either OM/AM 40/10 mg or PER 8 mg (2x4 mg) plus AM 10 mg and will be administered once daily. Furthermore, open-label HCTZ 12.5 mg and 25.0 mg will be provided in tablets and administered once daily according to the treatment schedule.

The primary endpoint is the change in central SBP from baseline (Week 0, Visit 0) to final examination (Week 24, Visit 5) using Last Observation Carried Forward (LOCF) approach.

The study is conducted in approximately 15 centres in Spain. Depending on the previously administered drugs the run in phase is up to four weeks (Visits -2 and -1). Individual duration of active treatment (after randomization) will last 24 weeks (Visits 0-5). The total individual duration is 28 weeks.

A total of 518 patients (259 patients/arm) will be needed in the Per Protocol Set (PPS) for the confirmatory primary analysis using mean change from baseline (Week 0) to Final Examination assuming a drop out rate of 20% during Run-in Phase a total of 720 patients have to be screened in order to achieve 576 (288 patients/arm) randomised patients.

Assuming approximately 10% major protocol deviations, a total of 518 patients will remain in the PPS.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 486
• Est. completion date: December 2012
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

Inclusion Criteria:

• moderate to severe hypertension

• 3 additional risk factors such as age > 55 (male), > 65 female, smoker, type 2 diabetes, obesity, cardiovascular disease, congestive heart failure, chronic kidney disease,

• ability to give informed consent

Exclusion Criteria:

• secondary or malignant hypertension

• contraindication to any of the study drugs

• Creatinine clearance level <40ml/min

• treatment with more than 3 antihypertensive drugs

• Myocardial infarction, percutaneous transluminal coronary angioplasty, cardiac bypass surgery < 6 month prior to start of the study,

• unstable angina pectoris,

• stroke, transient ischemic attack < 3 months prior to start,

• Congestive heart failure NYHA II-IV,

• clinically relevant concomitant diseases,

• alcohol or drug abuse,

• pregnancy or women of childbearing potential without contraceptive precaution,

Related Conditions & MeSH terms

• Hypertension

Intervention

Drug:
• Perindopril + amlodipine + if necessary, hydrochlorothiazide
Two perindopril 4 mg tablets + 1 amlodipine 10 mg tablet + placebo tablet matching the olmesartan/amlodipine tablet. All tablets are taken once daily. The duration of administration of perindopril tablets and placebo is 24 weeks. The duration of administration of amlodipine tablets is 24-26 weeks. Hydrochlorthiazide tablets 12.5 mg or 25 mg, once daily, will be added, if necessary
• olmesartan/amlodipine + hydrochlorothiazide, if necessary.
olmesartan/amlodipine tablets 40 mg/10 mg, + placebo tablets matching the perindopril tablet and amlodipine tablet. All tablets are taken once daily for 24 weeks. Hydrochlorthiazide tablets 12.5 mg or 25 mg, once daily, will be added, if necessary

Locations

Country	Name	City	State
Spain	Centro de Salud Casas Ibañez	Albacete
Spain	Hospital del Mar	Barcelona
Spain	Hospital General de Jerez de la Frontera	Cadiz
Spain	Hospital Universitario de Fuenlabrada	Fuenlabrada (Madrid)
Spain	Hospital General Universitario La Paz	Madrid
Spain	Hospital Universitario 12 Octubre	Madrid
Spain	Hospital Universitario Clínico San Carlos	Madrid
Spain	Hospital Universitario de Móstoles	Madrid
Spain	Hospital Universitario La Princesa	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	Hospital General Carlos Haya	Malaga
Spain	Centro de Salud Murcia San Andrés	Murcia
Spain	Hospital de Sagunto	Puerto De Sagunto (Valencia)
Spain	Centro de Salud La Alamedilla	Salamanca
Spain	Hospital Virgen de la Macarena	Sevilla

Sponsors (1)

Lead Sponsor	Collaborator
Daiichi Sankyo Europe, GmbH, a Daiichi Sankyo Company

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in central systolic blood pressure from baseline (Week 0, Visit 0) to Final Examination (Week 24, Visit 5) using last observation carried forward approach.		Baseline to week 24
Secondary	Changes in systolic and diastolic ambulatory blood pressure (mean of 24h, daytime and night-time)		Baseline to week 24
Secondary	Changes in conventional mean sitting systolic and diastolic blood pressure measurement		Baseline to 24 weeks
Secondary	Incidence and profile of AEs separately by Run-in Phase and by double-blind Treatment Phase		Run in phase (2 weeks) to end of study (24 weeks)
Secondary	Number of responders at Final Examination defined as normalized or a decrease of systolic blood pressure by at least 20 mmHg or diastolic blood pressure by at least 10 mmHg in conventional BP measurements.		Baseline to 24 weeks
Secondary	Number of normalized at Final Examination (defined as blood pressure <140/90 mmHg or <130/80 mmHg in diabetics/chronic kidney disease, in conventional BP measurements.		Baseline to 24 weeks
Secondary	Changes in mean sitting systolic and diastolic blood pressure (BP) measurements from week 12 to Final Exam in patients with stabilized BP (BP is < 140/90 mmHg or < 130/80 mmHg for diabetics/chronic kidney disease) from Week 12 and Week 18.		Week 12 to Week 18 or week 24
Secondary	Changes in Central Systolic Blood Pressure from week 12 to Final Examination in patients with stabilised BP (i.e. patients whose BP is < 140/90 mmHg or < 130/80 mmHg for diabetics/chronic kidney disease) between Week 12 and Week 18.		Week 12 to week 18 or week 24